[Role of HLA-DR and HLA-DQ alleles in multibacillary leprosy and paucibacillary leprosy in the province of Chaco (Argentina)]. / Papel de las moléculas HLA-DR y HLA-DQ en la lepra multibacilar y paucibacilar en la provincia del Chaco; Argentina.

OBJECTIVES: Segregation analyses in several populations have suggested a relationship between specific human leukocyte antigen (HLA) class II alleles and the development of different types of leprosy. The aim of this study was to determine the frequency of HLA class II DR and DQ alleles among leprosy patients in Chaco province, northeast Argentina, in an effort to determine whether these alleles might be involved in the development of the multibacillary (MB) and paucibacillary (PB) forms of leprosy. PATIENTS AND METHODS: Samples from 89 leprosy patients (MB = 70, PB = 19) and 112 healthy control subjects were analyzed. The HLA-DRB1 and HLA-DQB1 alleles were determined by PCR amplification and reverse hybridization with sequence-specific oligonucleotide probes, and analyzed with the INNO-LiPA typing system and LiPA software. DQB1*0201/0202/0203 in patients with MB leprosy and DRB1*04 in patients with PB leprosy were detected at significantly lower frequencies as compared with the normal controls. RESULTS: These data indicate that DQB1* 0201/0202/0203 may be a protective factor in MB leprosy and DRB1*04 in PB leprosy. DISCUSSION: We attribute the differences between our findings and those of other authors to the fact that the Caucasian inhabitants of Chaco include a considerable mixture of South American natives (Guaraníes and Tobas).

Papel de las moléculas HLA-DR y HLA-DQ en la lepra multibacilar y paucibacilar en la provincia del Chaco; Argentina / Role of HLA-DR and HLA-DQ alleles in multibacillary leprosy and paucibacillary leprosy in the province of Chaco (Argentina)

Objetivo. En la lepra, el análisis de segregación en varias poblaciones humanas sugiere una relación de alelos particulares de los antígenos leucocitarios humanos (HLA) clase II con el desarrollo de las diferentes formas de la enfermedad. Con el objetivo de determinar si algún alelo de las moléculas de HLA clase II en la población de la provincia del Chaco, Argentina, podrían estar comprometidos en el desarrollo de algunas de las formas de lepra multibacilar (MB) y/o paucibacilar (PB), se determinó la frecuencia de los alelos de los loci DR y DQ en pacientes con lepra. Pacientes y métodos. Se analizaron 89 muestras de pacientes con lepra (MB 5 70; PB 5 19) y 112 controles sanos. Se determinaron los alelos del locus DR y DQ, utilizando amplificación genérica por reacción en cadena de la polimerasa (PCR) e hibridación reversa con oligonucleótidos específicos (LIPA KEY-INNOGENETICS). Se encontró una disminución en la frecuencia del alelo DQB1*0201/0202/0203 en pacientes con lepra multibacilar y disminución del alelo DRB1*04 en pacientes con lepra paucibacilar respecto a controles, ambos con significación estadística. Resultados. Según los resultados observados, DQB1*0201/0202/0203 podría ser un alelo de protección en la forma multibacilar de la lepra y el alelo DRB1*04 estaría relacionado con protección en lepra paucibacilar. Discusión. Pensamos que las diferencias halladas con otras poblaciones caucásicas reportadas por otros autores se deben a que la población chaqueña de origen caucásico tiene una fuerte mezcla con nativos de América del Sur, guaraníes y tobas (AU)

Objectives. Segregation analyses in several populations have suggested a relationship between specific human leukocyte antigen (HLA) class II alleles and the development of different types of leprosy. The aim of this study was to determine the frequency of HLA class II DR and DQ alleles among leprosy patients in Chaco province, northeast Argentina, in an effort to determine whether these alleles might be involved in the development of the multibacillary (MB) and paucibacillary (PB) forms of leprosy. Patients and methods. Samples from 89 leprosy patients (MB 5 70, PB 5 19) and 112 healthy control subjects were analyzed. The HLA-DRB1 and HLA-DQB1 alleles were determined by PCR amplification and reverse hybridization with sequence-specific oligonucleotide probes, and analyzed with the INNO-LiPA typing system and LiPA software. DQB1*0201/0202/0203 in patients with MB leprosy and DRB1*04 in patients with PB leprosy were detected at significantly lower frequencies as compared with the normal controls. Results. These data indicate that DQB1* 0201/0202/0203 may be a protective factor in MB leprosy and DRB1*04 in PB leprosy. Discusion. We attribute the differences between our findings and those of other authors to the fact that the Caucasian inhabitants of Chaco include a considerable mixture of South American natives (Guaraníes and Tobas) (AU)

Association of HLA antigens with differential responsiveness to Mycobacterium w vaccine in multibacillary leprosy patients.

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness to Mycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium, Mycobacterium w, which has cross-reactive antigens with M. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8 + 9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to the M. w vaccine. However, these associations were not significant after P correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness to M. w vaccine.

Human leukocyte antigen and leprosy: study in northern Louisiana and review.

We examined the relationship of human leukocyte antigen (HLA) phenotype to leprosy in six sporadic cases in northern Louisiana and in the world literature through pooling of the results of several studies. We found that HLA antigens DR2 and DQwl were associated with leprosy in the six cases in northern Louisiana (relative risks, 4.57 for DR2 and 4.53 for DQwl), but the results are not statistically significant. We pooled the Louisiana study and other population studies of HLA and leprosy. The results of the pooling show DR2 and DQwl to be associated with leprosy (relative risks, 2.65 for DR2 and 2.73 for DQwl), and these associations are highly statistically significant (P less than 1 x 10(-8) for DR2 and P = 3.6 x 10(-8) for DQwl). Further, we pooled studies of lepromatous leprosy patients vs. controls and studies of tuberculoid leprosy patients vs. controls and found that DR2 and DQwl are associated with both the lepromatous and the tuberculoid forms of leprosy and that these associations are statistically significant. We consider the associations of DR2 and DQwl in these population studies to be evidence for an HLA-associated genetic influence on susceptibility to leprosy.

HLA antigens and neural reversal reactions in Ethiopian borderline tuberculoid leprosy patients.

Reversal reactions (RR) or acute neuritis episodes are frequently observed in borderline tuberculoid (BT) leprosy patients during the first year of treatment, and are associated with a rapid increase in cell-mediated immunity. Because HLA-linked genes have been shown to be an important factor in determining the type of leprosy that develops in susceptible individuals and because HLA molecules regulate cellular interactions in the immune system, we have investigated whether RR are associated with HLA antigens in Ethiopian patients. The data reported here indicate that this is not the case: no significant differences in the distribution of HLA class I and class II antigens were observed among three groups: 28 BT patients with a history of RR, 27 BT patients with no history of RR, and 33 healthy individuals. In contrast to these negative results, we observed that HLA-DR3 was associated with high skin-test responsiveness against Mycobacterium leprae antigens among RR patients. Since DR3 was not associated with RR per se, the observed DR3-associated high responsiveness to M. leprae may not be primarily related to the development of RR.